Di-(2-ethylhexyl) phthalate inhibits expression and internalization of transthyretin in human placental trophoblastic cells.

During pregnancy, fetal thyroid hormones (THs) are dependent on maternal placental transport and their physiological level is crucial for normal fetal neurodevelopment. Earlier research has shown that Di-(2-ethylhexyl) phthalate (DEHP) disrupts thyroid function and THs homeostasis in pregnant women and fetuses, and affects placental THs transport. However, the underlying mechanisms are poorly understood. The present study, therefore, aimed to systematically investigate the potential mechanisms of DEHP-induced disruption in the placental THs transport using two human placental trophoblastic cells, HTR-8/SVneo cells and JEG-3 cells. While the exposure of DEHP at the doses of 0-400 µM for 24 h did not affect cell viability, we found reduced consumption of T3 and T4 in the culture medium of HTR-8/Svneo cells treated with DEHP at 400 µM. DEHP treatment did not affect T3 uptake and the expression of monocarboxylate transporters 8 (MCT8) and organic anion transporters 1C1 (OATP1C1). However, DEHP significantly inhibited transthyretin (TTR) internalization, down-regulated TTR, deiodinase 2 (DIO2), and thyroid hormone receptors mRNA expression and protein levels, and up-regulated deiodinase 3 (DIO3) protein levels in a dose-dependent manner. These results indicate that DEHP acts on placental trophoblast cells, inhibits its TTR internalization, down-regulates TTR expression and affects the expression of DIO2, DIO3, and thyroid hormone receptor. These may be the mechanisms by which PAEs affects THs transport through placental.

The levels of phthalate exposure and associations with obesity in an elderly population in China.

BACKGROUND: Few epidemiological studies on the correlation between phthalate exposure and elderly obesity in China are available. The purpose of the present study is to assess phthalate exposure levels and explore the connections between exposure to phthalates and obesity using a sample of Chinese community-dwelling elderly individuals. METHODS: Data were acquired from the baseline survey of the Cohort of Health of Elderly and Controllable Factors of Environment, which was established in Lu'an, Anhui province, China, from June to September in 2016. Urine samples were obtained to analyze the concentrations of seven phthalate metabolites, utilizing a high-performance liquid chromatography-tandem mass spectrometry method. General obesity was determined based on body mass index, and abdominal obesity based on waist circumference. Binary logistic regression models were utilized to analyze the associations of creatinine-corrected phthalate metabolite concentrations (categorized into quartiles) with general and abdominal obesity in elderly people. Moreover, a stratified analysis was performed to explore the difference between genders. RESULTS: Of 942 elderly individuals, 52.9% were defined as generally obese and 75.5% as abdominally obese. The detection rates of seven phthalate metabolites ranged from 90.07% to 99.80%. The highest median concentration was 44.08 µg/l (for MBP), and the lowest was 0.55 µg/l (for MEHP). The level of exposure to LMW(low-molecular-weight) PAEs is higher than that to HMW(high-molecular-weight) PAEs. After adjustment for confounding variables, we found a significant association between urinary MEOHP (mono-2-ethyl-5-oxohexyl phthalate), MEHP (mono-2-ethylhexyl phthalate), MBP (mono-n-butyl phthalate), MEP (mono-ethyl phthalate), and MMP (mono-methyl phthalate) levels and general obesity. MBP levels were also correlated with abdominal obesity. When stratified by gender, higher urinary levels of MEOHP, MBP, MEP, and MMP were associated with general obesity in males, whereas MBP and MMP levels were eminently correlated with general obesity in females. Higher urinary MBP levels were associated with increased abdominal obesity rates in males, but not in females. CONCLUSIONS: In conclusion, higher phthalate metabolite concentrations were correlated with obesity in the elderly. Moreover, a gender difference was observed in these associations.